This paper describes how socio-ecological theory and a syndemic health systems and public health approach may help address the plight of youth in situations of political violence and humanitarian emergencies. We describe the treatment gap caused by discrepancies in epidemiological prevalence rates, individual and family needs, and available human and material resources. We propose four strategies to develop a participatory public health approach for these youth, based on principles of equity, feasibility, and a balance between prevention and treatment. The first strategy uses ecological and transgenerational resilience as a theoretical framework to facilitate a systems approach to the plight of youth and families. This theoretical base helps to engage health care professionals in a multisectoral analysis and a collaborative public health strategy. The second strategy is to translate pre-program assessment into mental health and psychosocial support (MHPSS) priorities. Defining priorities helps to develop programs and policies that align with preventive and curative interventions in multiple tiers of the public health system. The third is a realistic budgetary framework as a condition for the development of sustainable institutional capacity including a monitoring system. The fourth strategy is to direct research to address the knowledge gap about effective practices for youth mental health in humanitarian settings.